Haishengsu, a Protein from Shellfish Tegillarca L. granosa, Inhibits the Growth and the Activity of Matrix Metalloproteinases-2 and -9 in Human Lung Carcinoma

Abstract

Haishengsu (HSS) is a seashell protein extracted from Tegillarca L. granosa, a type of Malaysian shellfish. Previous in vitro studies showed that HSS might possess biological anticancer activity. In this combined in vitro and in vivo study, we investigated the inhibitory effects of HSS on tumor growth, invasion, and metastasis using human lung carcinoma cell lines A549 and NCI-H292, both intensely positive for matrix metalloproteinases-2 (MMP-2) and MMP-9. HSS significantly inhibited the proliferation of A549 and NCI-H292 as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The transwell chamber assay showed that HSS effectively blocked the invasion and migration of the carcinoma cells through the reconstituted extracellular matrix (Matrigel). Gelatin zymography analysis revealed that the secretion and activity of MMP-2 and MMP-9 in the supernatants of the cultured cells A549 and NCI-H292 were decreased after treatment with HSS. The levels of MMP-2 and MMP-9 in these cancer cells were further examined by Western blot assay in which a significant decrease of MMP-2 and MMP-9 was observed in A549 and NCI-H292 cells after 24 h of exposure to HSS. The anticancer activity of HSS was verified in a mouse model in which HSS delayed the growth of A549 xenografts after 3 weeks of oral administration. Inhibition of MMP-2 and MMP-9 expression was also demonstrated in the A549 xenografts as determined by Western blot analysis. These results suggest that HSS is a novel seashell protein that cannot only inhibit tumor growth but also prevent tumor invasion and metastasis through suppressing the activity of MMP-2 and MMP-9.

Tegillarca granosa Extract Haishengsu Induces Apoptosis in Human Hepatocellular Carcinoma Cell Line BEL-7402 Via Fas-Signaling Pathways

“…HSS has a potential cytotoxic effect on human ovarian cancer cells (SKOV-3 and OVCAR-3), which was mediated by multiple signal molecules including bcl-2, caspase-3, b-catenin, and CD24 [17]. HSS possesses a capacity to inhibit the growth of human lung carcinoma cells (A549 and NCI-H292) by suppressing the activities and expressions of MMP-2 and MMP-9 [21]. The growths of transplanted K562 and K562/ADM tumors were inhibited in the presence of HSS in mice [18].…”

“…Haishengsu (HSS) is an extract isolated from T. granosa, and its major chemical constituents are proteins with a molecular weight ranging from 15 to 23 kDa. Our previous experimental result indicated that HSS displayed substantial potential inhibitory effects on several types of cancer cell lines including human ovarian cancer cells SKOV-3 and OVCAR-3 [17], human leukemic cells K562 and K562/A02 [18][19][20], and human lung carcinoma cells A549 and NCI-H292 [21]. The aim of the present research was to study the apoptosisinducing activity of HSS in human hepatocellular carcinoma BEL-7402 cells and investigate the underlying mechanism.…”

Effects of high pressure on biochemical properties and structure of myofibrillar protein from Tegillarca granosa

“…It is rich in n‐3 polyunsaturated fatty acid (28.7–37.0% of total fatty acids) and contains predominantly high contents of DHA and EPA (7.9‐17.4%) (Nguyen et al , ). Its protein also contains substances that can prevent tumours (Liu et al , ; Chi et al , ). Furthermore, it is rich in blood, which is different from many other types of shellfish.…”

Purification and Partial Characterization of a New Antitumor Protein from Tegillarca granosa

“…T. granosa has been well researched in the field of genetics, which includes cDNA cloning and gene expression, as well as the functional study on the immune expression of hemoglobin gene [12]. In recent years, it has been reported that T. granosa extracts contained several active protein components [13], with diverse activities against fatigue [14], coagulation [15] and tumor growth [16,17]. Despite these findings, the purified protein with antitumor activity from T. granosa has not been reported.…”